RESUMO
Rearrangement of the mixed lineage-leukemia gene (MLL-r) is common in hematological diseases and is generally associated with poor prognosis. The mixed-lineage leukemia gene translocated to, 3 (MLLT3) gene (9p22) is a frequent MLL-r partner (â¼18% of leukemias with MLL rearrangement) and is characterized by the translocation t(9;11) (p22;q23), forming an MLL-MLLT3 gene fusion. MLL-r are usually simple reciprocal translocations between two different chromosomes, although karyotypes with complex MLL-r have been observed. We present a rare case of a child with acute lymphoblastic leukemia with a complex karyotype in which the classical t(9;11) (p22;q23) was cryptically relocated into a third chromosome in a balanced three-way translocation. At the genome level, however, the MLL-MLLT3 three-way translocation still displayed both reciprocal fusion transcripts. This argues in favor for a model where a simple two-way t(9;11) (p22;q23) was likely the first step that then evolved in to a more complex karyotype. Multicolor banding techniques can be used to greatly refine complex karyotypes and its chromosomal breakpoints. Also in the presence of putative new rearrangements, Long distance inverse-PCR is an important tool to identify which gene fusion is involved.
Assuntos
Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pré-Escolar , Feminino , Humanos , Cariótipo , Translocação GenéticaRESUMO
About 95% of HTLV-1 infected patients remain asymptomatic throughout life, and the risk factors associated with the development of related diseases, such as HAM/TSP and ATL, are not fully understood. The human leukocyte antigen-G molecule (HLA-G), a nonclassical HLA class I molecule encoded by MHC, is expressed in several pathological conditions, including viral infection, and is related to immunosuppressive effects that allow the virus-infected cells to escape the antiviral defense of the host. The 14-bp insertion/deletion polymorphism of exon 8 HLA-G gene influences the stability of the transcripts and could be related to HTLV-1-infected cell protection and to the increase of proviral load. The present study analyzed by conventional PCR the 14-bp insertion/deletion polymorphism of exon 8 HLA-G gene in 150 unrelated healthy subjects, 82 HTLV-1 infected patients with symptoms (33 ATL and 49 HAM), and 56 asymptomatic HTLV-1 infected patients (HAC). In addition, the proviral load was determined by quantitative real-time PCR in all infected groups and correlated with 14-bp insertion/deletion genotypes. The heterozygote genotype frequencies were significantly higher in HAM, in the symptomatic group, and in infected patients compared to control (p < 0.05). The proviral load was higher in the symptomatic group than the HAC group (p < 0.0005). The comparison of proviral load and genotypes showed that -14-bp/-14-bp genotype had a higher proviral load than +14-bp/-14-bp and +14-bp/+14-bp genotypes. Although HLA-G 14-bp polymorphism does not appear to be associated with HTLV-1 related disease development, it could be a genetic risk factor for susceptibility to infection.
Assuntos
Infecções por Deltaretrovirus/genética , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Mutação INDEL , Polimorfismo Genético , Adolescente , Adulto , Idoso , DNA Viral/genética , Suscetibilidade a Doenças , Feminino , Genótipo , Antígenos HLA-G , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de Risco , Carga Viral/genéticaRESUMO
OBJETIVO: Analisar a tendência de mortalidade por leucemias na infância, no estado do Rio de Janeiro, durante o período de 1980 a 2006. MÉTODO: Foram utilizados os dados de mortalidade por leucemia em menores de 15 anos do Sistema de Informações de Mortalidade do Ministério da Saúde para os anos de 1980 a 2006, segundo o sexo, dos residentes de três áreas: município do Rio de Janeiro (capital), região metropolitana (exceto capital) e interior do estado. Foram considerados como óbitos por leucemia aqueles cuja causa básica havia sido codificada de acordo com a Classificação Internacional de Doenças, revisão 9 (CID-9), no período de 1980 a 1995, e segundo a CID-10 no período de 1996 a 2006. As taxas de mortalidade foram calculadas por faixa etária e ano de óbito, sendo, em seguida, ajustadas pela população mundial. Para análise de tendência, optou-se pelos modelos de regressão linear polinomial. Foi considerado um nível de significância de 5 por cento. RESULTADOS: As análises de tendência nas três localidades apresentaram perfis semelhantes, com um padrão decrescente e constante. Entretanto, a capital apresentou a maior queda em suas taxas. Analisando a tendência das taxas de mortalidade por leucemia infantil segundo o sexo, foi observado que, no sexo masculino, a incidência foi maior quando comparada ao sexo feminino nas três localidades analisadas. CONCLUSÃO: Foi observada uma tendência de declínio da mortalidade por leucemias na infância no estado do Rio de Janeiro, sendo mais acentuada na capital do que na região metropolitana e no interior do estado.
OBJECTIVE: To analyze trends in childhood leukemia mortality in the state of Rio de Janeiro, Brazil, between 1980 and 2006. METHOD: Gender-stratified leukemia mortality data for children aged < 15 years from 1980 to 2006 were retrieved from the Brazilian Mortality Information System for the state of Rio de Janeiro. Data were stratified by place of death (city of Rio de Janeiro proper, the state capital; Rio de Jane iro Metropolitan Region, excluding the capital; and rest of the state). Leukemia deaths were defined according to death certificate ICD-9 and ICD-10 coding (for deaths occurring in 1980-1995 and 1996-2006, respectively). Leukemia mortality rates were calculated by age and calendar year and age-adjusted to a standard world population. Polynomial linear regression with a 5 percent significance level was used to evaluate mortality trends in the study regions. RESULTS: The three studied regions revealed similar trends, with a continuous downward pattern; the most substantial decline was detected in the municipality of Rio de Janeiro (city proper). In all studied areas, leukemia mortality was highest among males. CONCLUSION: A downward trend in childhood leukemia mortality was detected throughout the state of Rio de Janeiro. The most pronounced reduction occurred in the state capital.
Assuntos
Criança , Feminino , Humanos , Masculino , Leucemia/mortalidade , Distribuição por Idade , Brasil/epidemiologia , Modelos Lineares , Mortalidade/tendências , Distribuição por SexoRESUMO
BACKGROUND: Children with Down syndrome (DS) have an increased risk of childhood acute leukemia, especially acute megakaryoblastic leukemia (AMKL) also called acute myeloid leukemia (AML) type M7. Here four yet unreported infants with such malignancies are reported. RESULTS: An unbalanced translocation involving chromosome 1 was identified by GTG banding in all cases. These were characterized in more detail by molecular cytogenetic approaches. Additional molecular analysis revealed in three of the four cases mutations in exon 2 of the GATA binding protein 1 (globin transcription factor 1), located in Xp11.23. CONCLUSION: Our results corroborate that abnormalities of chromosome 1 are common in DS-associated AMKL. Whether this chromosomal region contains gene(s) involved in hematopoietic malignant transformation remains to be determined.
RESUMO
We report the case of a five-month-old black male infant who had recurrent episodes of respiratory infections and also presented anemia and enlargements of the spleen, liver and lymphnodes. Hematological analysis revealed morphological abnormalities with megaloblastic dyserythropoiesis, while fetal hemoglobin assaying showed normal levels. Conventional and molecular cytogenetic analysis revealed monosomy of chromosome 7. Despite all therapeutic efforts during allogenic bone marrow transplantation, the child died due to generalized infection. The clinical and genetic distinctions between monosomy 7 syndrome and myelodysplastic disorders in childhood are discussed.
Assuntos
Humanos , Masculino , Lactente , Monossomia , Síndromes Mielodisplásicas , Transtornos Mieloproliferativos , Análise Citogenética , LeucemiaRESUMO
A 64-year-old woman is reported with Stage I (Rai) chronic lymphocytic leukaemia (CLL), in whom hypercalcemia developed when an increased proportion of prolymphocytic cells characterized a transformation of CLL in prolymphocytoid leukaemia (CLL/PL). Although hypercalcemia is more frequently found in T-cell leukaemia associated with human T lymphotropic lymphocyte type I, scattered reports indicate that patients with B-CLL can also be affected with this metabolic disturbance. The case described here, progressed with an indolent course of CLL for 26 months, when she was admitted with a very aggressive disease characterized by a high WBC count, splenomegaly and hypercalcemia. Despite an effort to achieve a clinical remission, she failed treatment and death was attributed to unresponsive hypercalcemia. The mechanism of hypercalcemia in such cases is unclear as no parathyroid adenoma or second malignant tumor was found ante mortem. This electrolytic disturbance would appear to be a direct consequence of the transforming leukaemia and a possible mechanism involving a secreted humoral factor that could lead to altered calcium metabolism.
Assuntos
Feminino , Humanos , Hipercalcemia , Leucemia Linfocítica Crônica de Células B/diagnósticoRESUMO
Já está bem estabelecido que as leucemias são grupos heterogeneos de neoplasias tanto do ponto de vista clínico como de seus aspectos biológicos. Com o advento de técnicas imunológicas, demonstrou-se que as leucemias agudas são modelos ideais para pesquisas que levam ao conhecimento mais profundo do sistema hematopoiético. Reconhecendo o valor de uma abordagem multidisciplinar para classificar e investigar a origem da célula leucêmica, nós descrevemos neste trabalho os conceitos morfológicos, citoquímicos, imunológicos, citogenéticos e moleculares mais utilizados nos estudos dessas neoplasias. Inicialmente, fizemos uma revisão dos princípios básicos e dos elementos que constituem o sistema hematopoiético, bem como dos mecanismos que podem originar a transformação malígna de uma linhagem celular. Descrevemos as diferenciações antigênicas das linhagens linfóides e mielóides, bem corno a metodologia que detecta moléculas específicas de subtipos celulares. Finalmente, selecionamos dez artigos publicados nos quais estão descritos nossa experiência na identificação e classificação de leucemias agudas e síndromes linfoproliferativas, utilizando urna abordagem multidiscinlinar conforme mencionada acima.
Leukemia has been recognized to be a hetereogeneous malignant disorder, both clinically and biologically. Acute leukemias have been at the forefront of clinicotherapeutic research providing models for understanding hemopoietic system and kinetcs of cell differentiation and malignant transformation. Recognizing the value of a multidisciplinary approach to the investigation of leukemic cell origin, we have described a study that encompasses morphology, cytochemistry, immunophenotyping, cytogenetics and molecular biology to characterize acute and peripheral leukemias. First, we have reviewed several statements of the biological principles which have led to a further understanding of hemopoiesis and possible mechanisms of leukemogenesis. Then we have described the basic concepts of current methodology that has been suggested as new approaches together with frequently used techniques to diagnose and classify leukemias. Finally, we selcted ten consecutive papers, that were published, describing our experience to identify and characterize acute undifferentiated leukemias and lymphoproliferative disorders, through multidisciplinary approaches.